Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

Szu Lee; Min Wu Chao; Yi Wen Wu; Chia Min Hsu; Tony Eight Lin; Kai Cheng Hsu; Shiow Lin Pan; Hsueh Yun Lee

doi:10.1039/d3ra06600b

Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

Szu Lee, Min Wu Chao, Yi Wen Wu, Chia Min Hsu, Tony Eight Lin, Kai Cheng Hsu, Shiow Lin Pan, Hsueh Yun Lee

Research output: Contribution to journal › Article › peer-review

Abstract

The K₂S₂O₈-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC₅₀ values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.

Original language	English
Pages (from-to)	31595-31601
Number of pages	7
Journal	RSC Advances
Volume	13
Issue number	45
DOIs	https://doi.org/10.1039/d3ra06600b
Publication status	Published - Oct 30 2023

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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10.1039/d3ra06600b

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title = "Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol",

abstract = "The K2S2O8-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC50 values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.",

author = "Szu Lee and Chao, \{Min Wu\} and Wu, \{Yi Wen\} and Hsu, \{Chia Min\} and Lin, \{Tony Eight\} and Hsu, \{Kai Cheng\} and Pan, \{Shiow Lin\} and Lee, \{Hsueh Yun\}",

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doi = "10.1039/d3ra06600b",

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T1 - Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

AU - Lee, Szu

AU - Chao, Min Wu

AU - Wu, Yi Wen

AU - Hsu, Chia Min

AU - Lin, Tony Eight

AU - Hsu, Kai Cheng

AU - Pan, Shiow Lin

AU - Lee, Hsueh Yun

PY - 2023/10/30

Y1 - 2023/10/30

N2 - The K2S2O8-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC50 values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.

AB - The K2S2O8-mediated generation of p-iminoquinone contributed to the regioselective substitution of isoquinolin-5,8-dione. This hydroxyl group-guided substitution was also applied to selected heterocycles and addressed the regioselectivity issue of quinones. This study has provided an expeditious pathway from isoquinolin-5-ol (5) to ellipticine (1) and isoellipticine (2), which benefits the comprehensive comparison of their activity. Compounds 1 and 2 displayed marked MYLK4 inhibitory activity with IC50 values of 7.1 and 6.1 nM, respectively. In the cellular activity of AML cells (MV-4-11 and MOLM-13), compound 1 showed better AML activity than compound 2.

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ER -

Synthesis and evaluation of potent (iso)ellipticine-based inhibitors of MYLK4 accessed via expeditious synthesis from isoquinolin-5-ol

Abstract

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